Phylogenetic and amino acid conservation analyses of bacterial l-aspartate-α-decarboxylase and of its zymogen-maturation protein reveal a putative interaction domain

BMC Research Notes

Jorge C Escalante-Semerena¹  Garret Suen³  Kelsey M Hodge-Hanson⁴  Shanti Bramhacharya²  Tara N Stuecker⁵ 

[1] Department of Microbiology, University of Georgia, 212C, Biological Sciences Building, 120 Cedar Street, Athens 30602, GA, USA;Microsoft Corporation, 7000 State Highway 161, Irving 75039, TX, USA;Department of Bacteriology, University of Wisconsin-Madison, Madison 53706, WI, USA;Department of Microbiology, University of Georgia, Biological Sciences Building, 120 Cedar Street, Athens 30602, GA, USA;Department of Biological Sciences, University of Arkansas, 850 W. Dickson St., SCEN 601, Fayettevile 72701, AR, USA

关键词: PanM;    Pro-PanD maturation;    Aspartate decarboxylase;    Beta-alanine;    Pantothenate;    Coenzyme A biosynthesis;    Pyruvoyl enzymes;    Zymogen processing;   

Others  :  1230882
DOI  :  10.1186/s13104-015-1314-6

 received in 2015-04-22, accepted in 2015-08-03,  发布年份 2015

【 摘 要 】

Background

All organisms must synthesize the enzymatic cofactor coenzyme A (CoA) from the precursor pantothenate. Most bacteria can synthesize pantothenate de novo by the condensation of pantoate and β-alanine. The synthesis of β-alanine is catalyzed by L-aspartate-α-decarboxylase (PanD), a pyruvoyl enzyme that is initially synthesized as a zymogen (pro-PanD). Active PanD is generated by self-cleavage of pro-PanD at Gly24-Ser25 creating the active-site pyruvoyl moiety. In Salmonella enterica, this cleavage requires PanM, an acetyl-CoA sensor related to the Gcn5-like N-acetyltransferases. PanM does not acetylate pro-PanD, but the recent publication of the three-dimensional crystal structure of the PanM homologue PanZ in complex with the PanD zymogen of Escherichia coli provides validation to our predictions and provides a framework in which to further examine the cleavage mechanism. In contrast, PanD from bacteria lacking PanM efficiently cleaved in the absence of PanM in vivo.

Results

Using phylogenetic analyses combined with in vivo phenotypic investigations, we showed that two classes of bacterial L-aspartate-α-decarboxylases exist. This classification is based on their posttranslational activation by self-cleavage of its zymogen. Class I L-aspartate-α-decarboxylase zymogens require the acetyl-CoA sensor PanM to be cleaved into active PanD. This class is found exclusively in the Gammaproteobacteria. Class II L-aspartate-α-decarboxylase zymogens self cleave efficiently in the absence of PanM, and are found in a wide number of bacterial phyla. Several members of the Euryarchaeota and Crenarchaeota also contain Class II L-aspartate-α-decarboxylases. Phylogenetic and amino acid conservation analyses of PanM revealed a conserved region of PanM distinct from conserved regions found in related Gcn5-related acetyltransferase enzymes (Pfam00583). This conserved region represents a putative domain for interactions with L-aspartate-α-decarboxylase zymogens. This work may inform future biochemical and structural studies of pro-PanD-PanM interactions.

Conclusions

Experimental results indicate that S. enterica and C. glutamicumL-aspartate-α-decarboxylases represent two different classes of homologues of these enzymes. Class I homologues require PanM for activation, while Class II self cleave in the absence of PanM. Computer modeling of conserved amino acids using structure coordinates of PanM and L-aspartate-α-decarboxylase available in the protein data bank (RCSB PDB) revealed a putative site of interactions, which may help generate models to help understand the molecular details of the self-cleavage mechanism of L-aspartate-α-decarboxylases.

【 授权许可】

   
2015 Stuecker et al.

【 图 表 】

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